Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport syst ....Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport systems located in the bacterial plasma membrane, beneath the cell wall, facilitating Zn uptake by the bacterium. The aim of this project is to conduct comprehensive molecular characterization of the interactions between Pht proteins, Zn and ABC transporters, and the role of the histidine triad motifs in these interactions.Read moreRead less
The development and evaluation of a new therapy for the prevention and treatment of bacterial infections in hospitals. The technology used in this project will enable products to be developed from the Australian dairy industry which may safely provide protection and treatment for diarrhoea acquired in hospitals for which there are few effective options. The product will be cost effective and can be used as a public health tool to control outbreaks in those most susceptible to severe disease.
Molecular characterisation of hypervirulence and the infectious cycle in Clostridium difficile. Gut diseases caused by the bacterium Clostridium difficile are a significant animal and public health problem in Australia and many other countries. This project will allow us to understand how this bacterium causes disease, leading to the development of much needed preventative and treatment strategies for animals and human patients.
Targeted isolation of specific marine bacterial species associated with higher organsims for the purpose of discovering new antimicrobial compounds. Specific bacterial species that are commonly found in association with marine plants and animals often produce active secondary metabolites. The aim of this project is to apply our understanding of these bacterial-host associations to the targeted isolation of novel antimicrobials from the marine environment. While these new compounds will undoubted ....Targeted isolation of specific marine bacterial species associated with higher organsims for the purpose of discovering new antimicrobial compounds. Specific bacterial species that are commonly found in association with marine plants and animals often produce active secondary metabolites. The aim of this project is to apply our understanding of these bacterial-host associations to the targeted isolation of novel antimicrobials from the marine environment. While these new compounds will undoubtedly have a number of commercial applications this project focuses on the development of products for dental hygiene in animals. Generally, the urgent need for new antimicrobial compounds to combat the growing number of microbes that are resistant to current antibiotics highlights the importance of this project.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100963
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
Biofilms and quorum sensing in pneumococcal biology. Bacteria survive in their environmental niches by development of complex multicellular communities (biofilms), not by operating as individuals. Communication between bacteria is critical for biofilm formation, and is linked to their capacity to exchange DNA within and between species (competence). This is achieved by secretion and detection of small chemical signalling molecules (quorum sensing). Two such systems operate in the pneumococcus, a ....Biofilms and quorum sensing in pneumococcal biology. Bacteria survive in their environmental niches by development of complex multicellular communities (biofilms), not by operating as individuals. Communication between bacteria is critical for biofilm formation, and is linked to their capacity to exchange DNA within and between species (competence). This is achieved by secretion and detection of small chemical signalling molecules (quorum sensing). Two such systems operate in the pneumococcus, a model Gram-positive organism. This project aims to elucidate the mechanism whereby these quorum sensing systems interact and collaborate to regulate biofilm formation and competence, phenotypes critical for bacterial survival. This knowledge will enable future development of novel antimicrobials. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200100111
Funder
Australian Research Council
Funding Amount
$373,097.00
Summary
Replication and transfer of novel plasmid classes in Acinetobacter. The project aims to reveal basic biology of plasmids found in Acinetobacter baumannii. A. baumannii is a bacterial pathogen that can rapidly acquire resistance to antibiotics, including last-resort antibiotics. In modern strains, acquisition is often mediated by plasmids. On the basis of DNA sequencing data, A. baumannii plasmids are likely to function differently to well-studied plasmids. However, surprisingly little experiment ....Replication and transfer of novel plasmid classes in Acinetobacter. The project aims to reveal basic biology of plasmids found in Acinetobacter baumannii. A. baumannii is a bacterial pathogen that can rapidly acquire resistance to antibiotics, including last-resort antibiotics. In modern strains, acquisition is often mediated by plasmids. On the basis of DNA sequencing data, A. baumannii plasmids are likely to function differently to well-studied plasmids. However, surprisingly little experimental work has been done to evidence this. By combining microbiological and bioinformatics approaches the project expects to generate new knowledge on the mechanisms of replication and transfer of A. baumannii plasmids. This may lead to new targets for strategies to slow and track the spread of antibiotic resistance.Read moreRead less
Generation and Exploitation of Fermentation Products in the Chemical Synthesis of Biologically Active Compounds with Therapeutic Potential. Dramatic developments in biotechnology have provided access to genetically engineered micro-organisms capable of effecting unusual transformations so as to form novel compounds of great value in chemical synthesis. This project will combine the powers of biotechnology with those of chemical synthesis to produce compounds that have therapeutic potential in th ....Generation and Exploitation of Fermentation Products in the Chemical Synthesis of Biologically Active Compounds with Therapeutic Potential. Dramatic developments in biotechnology have provided access to genetically engineered micro-organisms capable of effecting unusual transformations so as to form novel compounds of great value in chemical synthesis. This project will combine the powers of biotechnology with those of chemical synthesis to produce compounds that have therapeutic potential in the treatment of Alzheimer's disease, cancer and viral infections.Read moreRead less
Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to tr ....Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to treat a range of pathogenic bacteria, including "Golden Staph".Read moreRead less
Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that ma ....Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that may represent targets for therapeutic intervention. Additionally a precise understanding of the mechanisms of secretion of anchorless proteins will have an important impact in the biotechnology field, as new methodologies for the secretion of recombinant proteins of industrial value is a potential outcome.Read moreRead less